Recruitment and investigation of moderate-size bipolar families for molecular genetic s the inheritance of bipolar (BP) illness has continued. We have concentrated on completing diagnostic work and obtaining all available blood samples on the families first identified in previous years. Nearly@, 150 blood samples and diagnostic interviews have been obtained this year. 24 families have been selected for systematic genomic mapping. These families (consisting of 485 persons, of whom 195 are affected with BP, unipolar [UP] or schizoaffective [SA] illnesses) represent 324 observable meioses, and include five pedigrees, each having 10 or more ill persons. Lymphoblastoid cell lines have been established for approximately 425 of these persons, 150 cell lines from this year. These cell lines will be used to screen the genome with evenly spaced DNA probes in a search for linkage. Mathematical simulations based on this pedigree series indicate that it has greater than 80% power to detect linkage (al I % recombination, assuming a marker heterozygosity of 70%) when 25% of these families are linked a , marker. Thus, this series of pedigrees can be used to detect a common genetic cause of bipolar disease. The search for large multiplex families of schizophrenic probands has continued, with two new families identified this year. This brings the total number of such families to I 1, consisting of 220 persons, 72 of whom are affected (schizoaffective or schizophrenic diagnoses). Lymphoblastoid cell lines have been established on 160 of these persons. A similar search for families of panic disorder probands has been initiated in collaboration with the Center for Behavioral Medicine. Thirteen probands with panic disorder, each of whom has at least five affected relatives, have been identified. Systematic evaluation of these families is currently being conducted. A longitudinal prospective study of adolescents at high risk for affective disorder has been continued. These offspring are being followed to determine whether predictors of illness can be identified.